Protein crystallization, whether for aqueous or membrane proteins, is a major bottleneck limiting determination of protein structure. A recent international survey of protein crystallization rates at 22 structural genomics centers around the world indicated that for 10,204 soluble proteins obtained, crystals were obtained for only 3,397 proteins. Of these 3,397 crystals, only 1,669 were of diffraction quality and a mere 1,352 structures were solved.
Several problems contribute to the low success rate described above for producing diffraction quality crystals. One involves the production of sufficient amounts of purified protein to be used in numerous crystallization experiments. Therefore, there is a need in the art for a method and apparatus to perform crystallization procedures using small amounts of protein. Second, is the ability to find the correct set of crystallization conditions for a particular protein. There are a huge number of variables that impact the crystallization process for a given protein. These factors include, but are not limited to: protein purity, protein dilution, protein homogeneity, protein stability, the flexibility of the protein itself, the selection of precipitating agent, the selection of buffer, the selection of pH, the selection of temperature, light, magnetism, gravity, atmosphere identity, atmospheric pressure, the selection of divalent anion, organic moment and the selection of additional additives to aid in crystallization. For membrane proteins, additional factors must be considered, such as, but not limited to, the type of lipid present, relative types and concentrations of detergent present, polar, apolar and amphipathic additives and limited protein quantity. Each of the above factors must be considered both alone and in combination, to determine a set of crystallization conditions that yield high quality diffracting crystals (i.e. optimal conditions). However, new high throughput testing systems have allowed scientists to test thousands of crystallization conditions for a given protein, suggesting that the large number of potential variables is not the only issue. Therefore, factors other than the multiplicity of crystallization conditions appear to be influencing the poor success rate of crystal production.
Therefore, the prior art is lacking and is in need of a method and apparatus to efficiently test and evaluate a wide range of crystallization conditions in the crystallization space for a given protein in order to determine crystallization conditions for said protein, and to test and evaluate a wide range of solubility conditions for a given protein in order to determine solubility conditions for said protein. In addition, it is also useful to determine solution conditions in which a protein will remain soluble e.g. solution condition that will not precipitate said protein.